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The multidrug resistance P-glycoprotein modulates cell regulatory volume decrease

M A Valverde1, T D Bond, S P Hardy

  • 1Nuffield Department of Clinical Biochemistry and Imperial Cancer Research Fund Laboratories, John Radcliffe Hospital, University of Oxford, UK.

The EMBO Journal
|September 2, 1996
PubMed
Summary
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Cell volume regulation involves anion channels. P-glycoprotein (P-gp) enhances cell volume decrease by speeding up chloride channel activation, aiding cells in hyposmotic conditions.

Area of Science:

  • Cellular physiology
  • Molecular biology
  • Membrane transport

Background:

  • Cell volume regulation is crucial for cellular homeostasis.
  • Swelling-activated chloride channels play a key role in regulatory volume decrease (RVD).

Purpose of the Study:

  • To investigate the role of swelling-activated chloride channels in RVD.
  • To determine the influence of P-glycoprotein (P-gp) on chloride channel activation and RVD.

Main Methods:

  • Patch-clamp technique to study ion channel activity.
  • Non-invasive microspectrofluorimetric assay for cell volume changes.
  • Gene expression analysis of MDR1/mdr1 genes encoding P-gp.

Main Results:

  • The rate of chloride channel activation limits the speed of RVD.

Related Experiment Videos

  • Expression of human MDR1 or mouse mdr1a (encoding P-gp) accelerated channel activation and RVD.
  • P-gp reduced the osmotic stress needed to activate channels and RVD.
  • Tamoxifen inhibited both chloride channel activity and RVD.

    • Conclusions:

    • Swelling-activated chloride channels are central to RVD in these cell types.
    • P-gp enhances RVD by modulating chloride channel activation.
    • P-gp improves cellular ability to down-regulate volume under hyposmotic stress.